Study Spots Gene That Plays Role in Infertility

THURSDAY Jan. 31, 2008 -- Scientists think they have discovered a mechanism that prompts early menopause and might account for some infertility problems in women.

PTEN -- a gene that's known for suppressing tumor growth -- apparently also keeps immature eggs in the ovary from ripening too quickly. When researchers deleted the PTEN gene in mice, the rodents ran out of their entire supply of eggs while they were still in the mouse equivalent of early adulthood. If ultimately applicable in humans, the revelation could lead to better infertility treatments.

"This finding is believed to have broad physiological, clinical and practical significance," said senior study author Kui Liu, an assistant professor of medical biochemistry and biophysics at Umea University, in Sweden. The report is published in the Feb. 1 issue of Science.

A woman's ovaries are made up of follicles, each of which contains an oocyte (the germ cell which will eventually give rise to an egg).

Over time, the majority of follicles remain dormant, acting as holding pens for immature oocytes. Some of these dormant follicles, however, slowly move over to the growing active follicle pool, where they are available for immediate release and, perhaps, fertilization. Menopause occurs when there are no more follicles and, therefore, no more oocytes left.

The length of a woman's reproductive life is determined by the size of her follicle pool and the rate at which this pool is depleted.

Until now, scientists have not completely understood what mechanisms are involved in this process.

For this study, Liu and colleagues deleted the PTEN gene in mice and found that these mice produced, at the most, one normal-sized litter after which they could no longer give birth. They were still in early adulthood (12 to 13 weeks of age) when they experienced this premature ovarian failure.

The same genetic variation may be responsible for premature ovarian failure in women, the authors stated. And manipulating the PTEN gene could hold hope for the future.

"Previously, it was not possible to use the sleeping primordial follicles for in vitro fertilization, as they are not able to grow up in a culture dish," Liu said. "Now that we know more about what is controlling the length of female fertility, it is also possible to culture a small slice of the ovary from an infertile woman, or a woman who will undergo chemo/radiation therapy, or an animal, and trigger the growth of primordial follicles in it by using synthetic PTEN inhibitors, and then further culture the follicles for in vitro fertilization. This means that a much richer resource of follicles can be used for in vitro fertilization."

Not only will humans potentially benefit, so might domestic animals and endangered animals that have difficulty breeding.

Future research, said Liu, will focus on finding good PTEN inhibitors.

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